ABSTRACT ? LIVER CANCER (LC) RESEARCH PROGRAM Program Leaders: Scott Friedman, MD and Josep Llovet, MD The Liver Cancer (LC) Program is a comprehensive multidisciplinary program that incorporates all aspects of the disease from community screening to fundamental mechanisms of heptocarcinogenesis in both hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC). The objectives of this program are to: 1) Elucidate fundamental mechanisms underlying the basis of how chronic liver or biliary disease and fibrosis precipitously increase the risk of HCC and ICC; 2) Translate these fundamental advances into novel approaches to the diagnosis and molecular stratification of HCC and ICC; 3) Test the efficacy of these novel interventions in investigator-initiated, early clinical proof-of concept trials and subsequently in pivotal randomized studies. The themes that have developed from this focus are: 1) Basic mechanisms of chronic hepatic inflammation that lead to HCC; 2) Molecular and cellular basis of hepatic fibrosis and HCC; 2) Novel models and pre-clinical studies of HCC pathogenesis and treatment; 3) Innovative therapeutic pre-clinical and clinical strategies for liver cancer (HCC and ICC). Highlights of the program include: a) Established comprehensive community outreach programs devoted to screening for chronic liver disease among underserved populations, linked to care for newly diagnosed liver disease; b) Unique clinical expertise in the preventive management of patients with chronic liver disease through hepatitis treatments and surgical care of HCC; c) A basic and translational research program that is redefining the molecular classification of HCC and ICC; d) A fruitful HCC tissue and serum bank that provides Mount Sinai scientists and investigators throughout the world with unique sets of genomic, proteomic and epigenetic data; e) A robust clinical trials program in HCC and ICC that has led the United States in enrollment in HCC clinical trials. The program is uniquely positioned to achieve its long-term goal to generate groundbreaking advances in understanding mechanisms of HCC and ICC, and to apply these towards the development and early testing of novel, personalized therapies that will improve the outlook for patients with these catastrophic malignancies The LC program has 24 members, and they represent 10 departments and 6 institutes. As of July 1, 2014, program members were awarded $3,124,363 in NCI and other peer-reviewed cancer-related direct support. Since 2011, LC program members published 220 reports, of which 28.6% were intra-programmatic and 8.2% inter-programmatic.